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Background: Dopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [(123)I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [(123)I]IBZM SPECT and the validity of the commonly employed single-scan pseudo-equilibrium analysis (PsEA) have not been appropriately investigated. The present study addresses these shortcomings., Methods: Ten movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [(123)I]IBZM injection. Kinetic analyses comprise: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2) and non-invasive graphical analysis (NIGA). Simplified single-scan analyses were performed at peak time of specific binding (peak-equilibrium analysis, PEA) and during pseudo-equilibrium (PsEA)., Results: SRTM and MRTM are compromised by the high noise level of dynamic SPECT. SRTM2 and MRTM2 yielded reliable binding potential estimates that agreed excellently (mean difference=-0.1+/-1.0%, R(2)>0.99). Concordance between SRTM/MRTM and SRTM2/MRTM2 was high in cases in which SRTM/MRTM provided reliable results (SRTM2 or MRTM2 vs. SRTM: 3.7+/-5.0%, R(2)=0.88). NIGA was affected by a negative bias (-9.1+/-6.3%, R(2)=0.75; MRTM2 as reference) or high variability (-1.2+/-7.4%, R(2)=0.71) for analyses without and with inclusion of the k(2)'-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6+/-10.8%, R(2)=0.59), which was considerably improved for PEA (-2.7+/-7.6%, R(2)=0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses., Conclusions: MRTM2 and SRTM2 can be reliably applied to dynamic [(123)I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).

Bactericidal/permeability-increasing protein (BPI) is an antineutrophil cytoplasmic autoantibody (ANCA) target antigen in inflammatory bowel disease (IBD). The aim of this study was to characterize binding regions of BPI-autoantibodies and to analyze their ability to block the antibiotic effect of BPI. Sera of 24 ulcerative colitis and Crohn's disease patients were examined in indirect immuno-fluorescence, ANCA enzyme-linked immunosorbent assay (ELISA), and by epitope mapping with 13mer peptides and Western blot for presence of BPI-autoantibodies. IgG preparations were used to determine inhibition of BPI's antimicrobial function by BPI-autoantibodies in a bacterial growth inhibition assay. BPI-autoantibodies were detected by ELISA in 18/24 patients. Epitope mapping and western blotting revealed an additional 3 patients with BPI-autoantibodies. IgG preparations of all patients with Crohn's disease and 9 of 12 ulcerative colitis patients could inhibit the antibiotic function of BPI in vitro as compared with healthy control subjects. Inhibiting BPI-autoantibodies correlated with extraintestinal manifestations, peripheral blood leukocyte counts, and anemia. BPI-autoantibodies recognizing the N-terminal portion were associated with greater mucosal damage and intestinal extent of disease. BPI is a frequent target antigen of autoantibodies in ulcerative colitis and Crohn's disease. Inhibition of the antibiotic function mediated by the N-terminal region of BPI by these autoantibodies may contribute to a proinflammatory environment in IBD patients.